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Phase 3 Study of Futuximab/Modotuximab in Combination With Trifluridine/Tipiracil Versus Trifluridine/Tipiracil Single Agent in Participants With Previously Treated Metastatic Colorectal Cancer (COLSTAR)

Primary Purpose

Metastatic Colorectal Cancer

Status
Terminated
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Futuximab/modotuximab
Trifluridine/Tipiracil
Trifluridine/Tipiracil
Sponsored by
Institut de Recherches Internationales Servier
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Metastatic Colorectal Cancer focused on measuring Futuximab/modotuximab, Trifluridine/tipiracil, Phase III, Safety Lead-In part, S95026, Sym004, Adult, Metastatic, Colorectal, Colorectal Cancer, EGFR

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Histologically or cytologically confirmed adenocarcinoma of metastatic colorectal cancer (mCRC), not amenable to surgical intervention due to either medical contraindications or non-resectability of the tumour without RAS (KRAS and NRAS) and BRAF V600E mutations based on Circulating tumour DNA (ctDNA) screening blood test analysis
  • Participants with measurable or non-measurable lesion
  • Participants must have received at least 2 prior regimens of standard chemotherapy for mCRC and had demonstrated progressive disease or intolerance to their last regimen
  • Participants should have received previous treatment with commercially available anti-EGFR mAbs for ≥ 4 months
  • Estimated life expectancy ≥ 12 weeks
  • Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
  • Adequate haematological, renal and hepatic function

Exclusion Criteria:

  • Pregnancy, possibility of becoming pregnant during the study, breastfeeding woman
  • Patients currently receiving or having received anticancer therapies within 4 weeks prior to the inclusion visit (Safety Lead-in part) or randomization visit (Phase 3 part).
  • Major surgery within 4 weeks prior to the inclusion visit (Safety Lead-in part) or randomization visit (Phase 3 part) or participants who have not recovered from side effects of the surgery
  • Participants with serious/active/uncontrolled infection
  • Known clinically significant cardiovascular disease or condition
  • Significant gastrointestinal abnormality
  • Skin rash of Grade > 1 from prior anti-EGFR at the time of inclusion (Safety Lead-in part) or randomization (Phase 3 part), or any other skin toxicity precluding participation in the study according to investigator's discretion.
  • Treatment with systemic immunosuppressive therapy within 4 weeks prior to inclusion (Safety Lead-in part) or randomization (Phase 3 part)
  • Prior radiotherapy if completed less than 4 weeks before the inclusion visit (Safety Lead-in part) or randomization visit (Phase 3 part)
  • Patients with other malignancies

Sites / Locations

  • University of Michigan Oncology Clinic | Rogel Cancer Center
  • Cleveland Clinic Cleveland Clinic Lerner College of Medicine
  • UZA Edegem
  • UZ Leuven Campus Gasthuisberg
  • CHUUCL Namur site Godinne
  • Rigshospitalet
  • Herning Regional Hospital (Regionhospitalet Godstrup)
  • Odense Universitetshospital
  • Docrates cancer center
  • TAYS (Tampere University Hospital)
  • National Cancer Center Hospital East

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Futuximab/modotuximab combined with trifluridine/tipiracil (Safety Lead-In and Phase III parts)

Trifluridine/tipiracil (Phase III part)

Arm Description

Outcomes

Primary Outcome Measures

Incidence of dose-limiting toxicities (DLTs) (Safety Lead-In part)
DLTs observed during a 28-day period
Overall Survival (OS) (In double negative, KRAS/NRAS and BRAF wild type patients) (Phase III part)
Time elapsed from date of randomization until the date of death from any cause

Secondary Outcome Measures

Overall survival (Safety Lead-In part)
Time elapsed from the first IMP intake to death
Overall survival (In triple negative) (Phase III part)
Time elapsed from the date of randomization into the study to disease progression/death
Progression Free Survival (Phase III part)
Time elapsed from the date of randomization into the study to disease progression/death
Adverse Events (Phase III part)
Incidence, severity, and relationship of treatment emergent adverse event and treatment emergent serious adverse event

Full Information

First Posted
January 25, 2022
Last Updated
September 13, 2023
Sponsor
Institut de Recherches Internationales Servier
Collaborators
ADIR, a Servier Group company
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1. Study Identification

Unique Protocol Identification Number
NCT05223673
Brief Title
Phase 3 Study of Futuximab/Modotuximab in Combination With Trifluridine/Tipiracil Versus Trifluridine/Tipiracil Single Agent in Participants With Previously Treated Metastatic Colorectal Cancer
Acronym
COLSTAR
Official Title
A Randomised, Open-label, Multi-centre, Two-arm Phase 3 Study Comparing Futuximab/Modotuximab in Combination With Trifluridine/Tipiracil to Trifluridine/Tipiracil Single Agent With a Safety Lead-In Part in Participants With KRAS/NRAS and BRAF Wild Type Metastatic Colorectal Cancer Previously Treated With Standard Treatment and Anti-EGFR Therapy
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Terminated
Why Stopped
Decision based on strategic reasons related to limited development options left in metastatic colorectal cancer.
Study Start Date
April 21, 2022 (Actual)
Primary Completion Date
June 21, 2023 (Actual)
Study Completion Date
June 21, 2023 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Institut de Recherches Internationales Servier
Collaborators
ADIR, a Servier Group company

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This is a randomized phase III study with a safety lead-in part in patients with KRAS/ NRAS and BRAF Wild Type metastatic colorectal cancer who have previously received treatment with oxaliplatin, irinotecan, fluoropyrimidines, anti-VEGF agents and anti-EGFR antibodies. The main objective of the safety lead-in part is to assess safety and tolerability of futuximab/modotuximab in combination with trifluridine/tipiracil. The primary objective of the phase III part is to compare Overall Survival of futuximab/modotuximab in combination with trifluridine/tipiracil vs trifluridine/tipiracil monotherapy in patients with tumours that are KRAS/NRAS and BRAF wild-type (WT) (Double negative [DN].

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Metastatic Colorectal Cancer
Keywords
Futuximab/modotuximab, Trifluridine/tipiracil, Phase III, Safety Lead-In part, S95026, Sym004, Adult, Metastatic, Colorectal, Colorectal Cancer, EGFR

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
7 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Futuximab/modotuximab combined with trifluridine/tipiracil (Safety Lead-In and Phase III parts)
Arm Type
Experimental
Arm Title
Trifluridine/tipiracil (Phase III part)
Arm Type
Active Comparator
Intervention Type
Biological
Intervention Name(s)
Futuximab/modotuximab
Intervention Description
Concentrate for solution for infusion, futuximab/modotuximab will be administered via IV route, once weekly of each cycle at 9 mg/kg/dose at Cycle 1 Day 1 and then at 6 mg/kg/dose. Each cycle is up to 28 days.
Intervention Type
Drug
Intervention Name(s)
Trifluridine/Tipiracil
Intervention Description
Film-coated tablets of trifluridine/tipiracil (35 mg/m²/dose) will be administered orally before futuximab/ modotuximab administration, twice a day (BID) within 1 hour after completion of morning and evening meals, 5 days on/2 days off, over 14 days, followed by a 14-day rest. This treatment cycle will be repeated every 28 days.
Intervention Type
Drug
Intervention Name(s)
Trifluridine/Tipiracil
Intervention Description
Film-coated tablets of trifluridine/tipiracil (35 mg/m²/dose) will be administered orally twice a day (BID) within 1 hour after completion of morning and evening meals, 5 days on/2 days off, over 14 days, followed by a 14-day rest. This treatment cycle will be repeated every 28 days.
Primary Outcome Measure Information:
Title
Incidence of dose-limiting toxicities (DLTs) (Safety Lead-In part)
Description
DLTs observed during a 28-day period
Time Frame
End of cycle 1 (Each cycle is up to 28 days)
Title
Overall Survival (OS) (In double negative, KRAS/NRAS and BRAF wild type patients) (Phase III part)
Description
Time elapsed from date of randomization until the date of death from any cause
Time Frame
up to 4 years 9 months
Secondary Outcome Measure Information:
Title
Overall survival (Safety Lead-In part)
Description
Time elapsed from the first IMP intake to death
Time Frame
up to 24 months
Title
Overall survival (In triple negative) (Phase III part)
Description
Time elapsed from the date of randomization into the study to disease progression/death
Time Frame
up to 4 years 9 months
Title
Progression Free Survival (Phase III part)
Description
Time elapsed from the date of randomization into the study to disease progression/death
Time Frame
up to 4 years 9 months
Title
Adverse Events (Phase III part)
Description
Incidence, severity, and relationship of treatment emergent adverse event and treatment emergent serious adverse event
Time Frame
Through study completion, up to 4 years 9 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Histologically or cytologically confirmed adenocarcinoma of metastatic colorectal cancer (mCRC), not amenable to surgical intervention due to either medical contraindications or non-resectability of the tumour without RAS (KRAS and NRAS) and BRAF V600E mutations based on Circulating tumour DNA (ctDNA) screening blood test analysis Participants with measurable or non-measurable lesion Participants must have received at least 2 prior regimens of standard chemotherapy for mCRC and had demonstrated progressive disease or intolerance to their last regimen Participants should have received previous treatment with commercially available anti-EGFR mAbs for ≥ 4 months Estimated life expectancy ≥ 12 weeks Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 Adequate haematological, renal and hepatic function Exclusion Criteria: Pregnancy, possibility of becoming pregnant during the study, breastfeeding woman Patients currently receiving or having received anticancer therapies within 4 weeks prior to the inclusion visit (Safety Lead-in part) or randomization visit (Phase 3 part). Major surgery within 4 weeks prior to the inclusion visit (Safety Lead-in part) or randomization visit (Phase 3 part) or participants who have not recovered from side effects of the surgery Participants with serious/active/uncontrolled infection Known clinically significant cardiovascular disease or condition Significant gastrointestinal abnormality Skin rash of Grade > 1 from prior anti-EGFR at the time of inclusion (Safety Lead-in part) or randomization (Phase 3 part), or any other skin toxicity precluding participation in the study according to investigator's discretion. Treatment with systemic immunosuppressive therapy within 4 weeks prior to inclusion (Safety Lead-in part) or randomization (Phase 3 part) Prior radiotherapy if completed less than 4 weeks before the inclusion visit (Safety Lead-in part) or randomization visit (Phase 3 part) Patients with other malignancies
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Fortunato Ciardiello
Organizational Affiliation
University of Campania "Luigi Vanvitelli"
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Michigan Oncology Clinic | Rogel Cancer Center
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States
Facility Name
Cleveland Clinic Cleveland Clinic Lerner College of Medicine
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Facility Name
UZA Edegem
City
Edegem
ZIP/Postal Code
2650
Country
Belgium
Facility Name
UZ Leuven Campus Gasthuisberg
City
Leuven
ZIP/Postal Code
3000
Country
Belgium
Facility Name
CHUUCL Namur site Godinne
City
Yvoir
ZIP/Postal Code
5530
Country
Belgium
Facility Name
Rigshospitalet
City
Copenhagen
ZIP/Postal Code
2100
Country
Denmark
Facility Name
Herning Regional Hospital (Regionhospitalet Godstrup)
City
Herning
ZIP/Postal Code
7400
Country
Denmark
Facility Name
Odense Universitetshospital
City
Odense
ZIP/Postal Code
5000
Country
Denmark
Facility Name
Docrates cancer center
City
Helsinki
ZIP/Postal Code
00180
Country
Finland
Facility Name
TAYS (Tampere University Hospital)
City
Tampere
ZIP/Postal Code
33520
Country
Finland
Facility Name
National Cancer Center Hospital East
City
Chiba
ZIP/Postal Code
277-8577
Country
Japan

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Qualified scientific and medical researchers can request access to anonymized patient-level and study-level clinical trial data. Access can be requested for all interventional clinical studies: used for Marketing Authorization (MA) of medicines and new indications approved after 1 January 2014 in the European Economic Area (EEA) or the United States (US). where Servier is the Marketing Authorization Holder (MAH). The date of the first MA of the new medicine (or the new indication) in one of the EEA Member States will be considered for this scope. In addition, access can be requested for all interventional clinical studies in patients: sponsored by Servier with a first patient enrolled as of 1 January 2004 onwards for New Chemical Entity or New Biological Entity (new pharmaceutical form excluded) for which development has been terminated before any Marketing authorization (MA) approval.
IPD Sharing Time Frame
After Marketing Authorisation in EEA or US if the study is used for the approval.
IPD Sharing Access Criteria
Researchers should register on Servier Data Portal and fill in the research proposal form. This form in four parts should be fully documented. The Research Proposal Form will not be reviewed until all mandatory fields are completed.
IPD Sharing URL
https://clinicaltrials.servier.com/
Links:
URL
https://clinicaltrials.servier.com/
Description
Find Results on Servier Clinical Trial Data website
Available IPD and Supporting Information:
Available IPD/Information Type
Individual Participant Data Set
Available IPD/Information URL
https://clinicaltrials.servier.com/
Available IPD/Information Type
Study Protocol
Available IPD/Information URL
https://clinicaltrials.servier.com/
Available IPD/Information Type
Statistical Analysis Plan
Available IPD/Information URL
https://clinicaltrials.servier.com/
Available IPD/Information Type
Informed Consent Form
Available IPD/Information URL
https://clinicaltrials.servier.com/
Available IPD/Information Type
Clinical Study Report
Available IPD/Information URL
https://clinicaltrials.servier.com/
Available IPD/Information Type
Study-level clinical trial data
Available IPD/Information URL
https://clinicaltrials.servier.com/

Learn more about this trial

Phase 3 Study of Futuximab/Modotuximab in Combination With Trifluridine/Tipiracil Versus Trifluridine/Tipiracil Single Agent in Participants With Previously Treated Metastatic Colorectal Cancer

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